Prevalence of EGFR gene mutations in patients with early-stage resectable non-small cell lung cancer in Spain: the ORIGEN study

Mar Varela; Cristina Teixidó; Carlos Álvarez-Fernández; Hugo Arasanz; Sergio Peralta; Martín Lázaro; Virginia Calvo; Rosa Álvarez; Javier Baena; Javier Valdivia; Edurne Arriola; Reyes Bernabé; Dolores Isla; Carmen Camacho; Bartomeu Massutí; Ana Blasco; Teresa García; Manuel Cobo; Marc Campayo; Sara Hijazo-Pechero; Ángel Callejo; Marta Domínguez; Ernest Nadal

doi:10.21037/tlcr-2024-1146

Prevalence of EGFR gene mutations in patients with early-stage resectable non-small cell lung cancer in Spain: the ORIGEN study

Transl Lung Cancer Res. 2025 Apr 30;14(4):1254-1265. doi: 10.21037/tlcr-2024-1146. Epub 2025 Apr 21.

Authors

Mar Varela^#¹, Cristina Teixidó^#², Carlos Álvarez-Fernández³, Hugo Arasanz⁴, Sergio Peralta⁵, Martín Lázaro⁶, Virginia Calvo⁷, Rosa Álvarez⁸, Javier Baena⁹, Javier Valdivia¹⁰, Edurne Arriola¹¹, Reyes Bernabé¹², Dolores Isla¹³, Carmen Camacho¹⁴, Bartomeu Massutí^{15

16

17}, Ana Blasco¹⁸, Teresa García¹⁹, Manuel Cobo²⁰, Marc Campayo²¹, Sara Hijazo-Pechero²², Ángel Callejo²³, Marta Domínguez²³, Ernest Nadal^{22

24

25}

Affiliations

¹ Department of Pathology, Catalan Institute of Oncology (ICO), Hospital Universitario de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
² Department of Pathology & CORE Biologia Molecular Centre de Diagnòstic Biomèdic, Hospital Clinic; Facultat de Medicina i Ciències Salut, Departament de Medicina, Universitat de Barcelona; Grup de Genòmica Translacional i Teràpies Dirigides en Tumors Sòlids, IDIBAPS, Barcelona, Spain.
³ Instituto de Investigación Sanitaria del Principado de Asturias, Hospital Universitario Central de Asturias, Oviedo, Spain.
⁴ Department of Medical Oncology, Hospital Universitario de Navarra, Navarra, Spain.
⁵ Department of Medical Oncology, Instituto de Oncología de la Cataluña Sur (IOCS), Tarragona, Spain.
⁶ Department of Medical Oncology, Instituto de Investigación Sanitaria Galicia Sur (IISGS), Vigo, Spain.
⁷ Department of Medical Oncology, Hospital Universitario Puerta de Hierro, Madrid, Spain.
⁸ Department of Medical Oncology, Instituto de Investigacion Sanitaria Gregorio Marañon, Hospital Universitario Gregorio Marañon, Madrid, Spain.
⁹ Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain.
¹⁰ Department of Medical Oncology, Hospital Universitario Virgen de las Nieves, Granada, Spain.
¹¹ Department of Medical Oncology, Hospital del Mar-CIBERONC, Barcelona, Spain.
¹² Department of Medical Oncology, Hospital Virgen del Rocio, Sevilla, Spain.
¹³ Department of Medical Oncology, University Hospital Lozano Blesa, Institute for Health Research Aragon (IIS Aragon), Zaragoza, Spain.
¹⁴ Department of Pathology, Complejo Hospitalario Universitario Insular Materno-Infantil, Servicio Canario de Salud, Las Palmas de Gran Canaria, Spain.
¹⁵ Department of Medical Oncology, Hospital Universitario Alicante Dr. Balmis, Alicante, Spain.
¹⁶ Grupo de Investigación Traslacional en Neoplasias Torácicas del Instituto de Investigación Sanitaria y Biomédica de Alicante ISABIAL, Alicante, Spain.
¹⁷ Facultad Medicina Universidad Miguel Hernández Elche, Elche, Spain.
¹⁸ Department of Medical Oncology, Hospital General Universitario de Valencia, CIBERONC, Valencia, Spain.
¹⁹ Department of Medical Oncology, Hospital Universitario Virgen Macarena, Sevilla, Spain.
²⁰ Medical Oncology Unit, Regional University Hospital, IBIMA, BIONAND, Málaga, Spain.
²¹ Department of Medical Oncology, Hospital Universitario de Terrassa, Barcelona, Spain.
²² Preclinical and Experimental Research in Thoracic Tumors (PRETT), Molecular Mechanisms and Experimental Therapy in Oncology Program (Oncobell), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
²³ Department of OBU Medical, AstraZeneca Farmacéutica Spain, Madrid, Spain.
²⁴ Department of Medical Oncology, Catalan Institute of Oncology (ICO), L'Hospitalet del Llobregat, Barcelona, Spain.
²⁵ Department of Clinical Sciences, University of Barcelona, Bellvitge Campus, L'Hospitalet del Llobregat, Barcelona, Spain.

^# Contributed equally.

Abstract

Background: Geographic variability in epidermal growth factor receptor (EGFR) mutation rates in early-stage non-small cell lung cancer (NSCLC) has been reported. However, the frequency of EGFR mutations in patients with early-stage resected NSCLC in Spain has not been previously investigated. We aimed to determine the prevalence of EGFR mutations in patients with early-stage resected NSCLC in Spain.

Methods: This was an observational, multicenter, cross-sectional study. Sensitizing EGFR mutations were assessed via real-time polymerase chain reaction (PCR)-based molecular analysis with the Idylla^TM EGFR Mutation Test, and next-generation sequencing (NGS) analysis with the Oncomine^TM Precision Assay.

Results: A total of 172 patients with surgically resected non-squamous NSCLC were analysed. Median age was 67.5 years and 57.6% were male, 96.5% had adenocarcinoma histology and 65% had stage IA/IB. EGFR mutations were found using Idylla^TM EGFR Mutation Test in 25 patients out of 172 patients (14.5%), which consisted of exon 19 deletion in 13 patients (7.6%), exon 21 L858R point mutation in 11 (6.4%), and exon 20 mutation (T790M) in 1 (0.6%) patient. The Oncomine^TM test was conducted in 128 patients, which detected exon 19 deletions in 10 patients (7.8%), exon 21 mutations in 10 patients (7.8%), and exon 20 insertions in 5 (3.9%) patients. The Oncomine^TM test was able to detect concurrent mutations in tumor suppressor genes (TP53, PI3KCA, CDKN2A, PTEN) and another actionable alteration beyond EGFR, such as mutations in KRAS G12C (22%), ERBB2 (6%), METex14 (2%), BRAF V600E (2%) and ALK and ROS1 fusions (2%, each).

Conclusions: The prevalence of EGFR mutations in early stage (IA-IIIB), resectable, non-squamous NSCLC observed in our study is consistent with that reported in advanced NSCLC in Spain. Molecular testing is crucial in early-stage NSCLC and can be performed either with single-gene testing or NGS.

Keywords: Non-small cell lung cancer (NSCLC); early stage; epidermal growth factor receptor mutations (EGFR mutations); molecular testing.